Rhythm Pharmaceuticals, Inc. Q4 FY2025 earnings call

• David Meagher discussed the Bivomelagon HO study, including the end of phase two meeting with the FDA, patient data at 40 weeks, and plans for phase three. - Jennifer Lee talked about the steady growth in BBS prescriptions, preparation for Acquired Hypothalamic Obesity launch, and engagement with HCPs and payers. - Jan Mazzebro mentioned the growth of the international organization, progress in acquired hypothalamic obesity in Europe and Japan, and publications related to early onset obesity. - Hunter Smith walked through the fourth quarter and full-year revenue results, inventory swing, and non-GAAP operating expenses guidance for 2026.

Revenues from sales of MCIVRI were $57.3 million for the fourth quarter of 2025, representing a quarter-over-quarter increase of 12% and $194.8 million for the full year, an increase of approximately 50% from 2024. In the fourth quarter of 2025, 39 million or 68% of product revenue was generated in the United States, and 18.3 million or 32% of product revenue was generated outside the United States. Net product revenues in Q4 2025 increased by $15.4 million, or 37%, over Q4 2024. Cost of goods sold this quarter was 8.5% of product revenue. Research and development expenses were $42 million for Q4 compared to $41.2 million in the same quarter last year. SG&A expenses were $57.5 million for Q4 2025 as compared to $38.1 million in Q4 last year.

• For 2026, anticipate approximately 385 million to 415 million in non-GAAP operating expenses, including non-GAAP R&D expenses of 197 million to 213 million and non-GAAP SG&A expenses of 188 million to 202 million. The increase is due to investments in formulation development, manufacturing, clinical supply of next-generation MC4 agonists, U.S. commercial operations for HO launch, and build-out in Japan.

Q: On divimelagons phase three, comments suggest trial will largely mimic set melanotide phase three, any changes to enrollment criteria?

A: No specific feedback from FDA on enrollment criteria changes, but may modify patient-reported outcome measures.

Q: On guidelines for HO for post-surgical patients, any comments?

A: Consensus is to intervene as soon as treating physician is comfortable.

Q: Update on PWS study?

A: Still on track for mid-year update, 17 of 18 patients remain on treatment, looking for 5% BMI change.

Q: On incivry trends and potential dampening of sales in 1Q?

A: Inventory represents pull forward of sales, typical Q1 has planned renewals and changes.

Q: On Emanate sub-studies, driven by enrollment and powering or genetic/biological?

A: POMC HETs most likely positive based on enrolling patients with true loss of function, leptin receptor cohort under-enrolled, SRC1 mostly variants of unknown significance, SH2B1 has groups with deletion and sense mutations.

Q: On BIVA study and 718 in same indication, how thinking?

A: 718 likely to have similar phase three requirements, quality control not issue, challenge is finding sites with good access to patients.

Q: On melatonin phase three trial dosing?

A: Dose escalate from 200 up to 600, 600 is target dose.

Q: On Japan investment and launch trajectory?

A: Estimated 5,000 - 8,000 patients, building team, affiliate, field medical team in place, data in March, launch in next 12 months.

Q: On AHO expansion launch cadence relative to BBS?

A: Similarities in opportunity and data dialogue, differences in precision of data to pinpoint right physicians and ability to identify patients earlier in journey.

Q: On sub 1.8 and Part D timelines, strategies to accelerate?

A: Regulators don't always agree with aggressive approach, 718 likely similar to Bivomelagon, next-gen in HO has urgency.

Q: On other MC4R development areas?

A: Early programs thinking about different approaches, will come back to specific genes with next-generation molecules.

Q: On MC4R M&A sub-studies regulatory path and BIVA HO-OLE results?

A: Sub-studies will be filed individually, in BIVA HO-OLE saw better results for patients not on GLP-1 as correcting underlying defect restores ability to respond to other anti-obesity medicine.

Q: On FDA review for acquired HO and supplementing data with Japanese cohort?

A: Yes, FDA aware of timing and will deal with including Japanese cohort data.

Q: On phase three for HO enrollment in U.S. and Prader-Willi trial?

A: Predominantly enroll outside U.S., for Prader-Willi, decision on set melanotide vs 718 yet to be made.

Q: On Biva dose selection and dosing down?

A: Targeted dose is 600, pathophysiology is hormonal deficiency, not likely to dose down as it's not biologic setting where that makes sense.